Cyanidin ameliorates cisplatin-induced cardiotoxicity via inhibition of ROS-mediated apoptosis

Abstract

Oxidative stress and apoptosis serve an essential role in cisplatin-induced cardiotoxicity, which limits its clinical use, and increases the risk of cardiovascular disease. As a natural drug, the antioxidant and antitumor effects of cyanidin have been recognized, but its protective effect on cisplatin-induced cardiomyocyte cytotoxicity remains unclear. H9c2 cells were treated with cisplatin (1–40 µM) in the presence or absence of cyanidin (40–80 µM), subsequently; oxidative stress, apoptosis and mitochondrial function were assessed using several techniques. The results demonstrated that cyanidin was able to dose-dependently reverse cisplatin-induced cell damage and apoptosis, attenuate the accumulation of reactive oxygen species (ROS), and mitochondrial membrane potential depolarization, downregulate the expression of Bcl-2 homologous antagonist/killer, upregulate the expression of apoptosis regulator Bcl-2, and reduce the activation of caspase 3, caspase 9, but not caspase 8. Furthermore, the results revealed that the translocation of apoptosis regulator Bax (Bax) from the cytoplasm to the mitochondrial membrane serves an essential role in cisplatin-induced apoptosis. Cyanidin was able to block the translocation of Bax and reduce the release of cytochrome c from cytoplasm. These data indicate that cyanidin attenuates cisplatin-induced cardiotoxicity by inhibiting ROS-mediated apoptosis, while the mitochondrial and extracellular regulated kinase signaling pathways may also serve important roles.

Protective effects of trimetazidine and coenzyme Q10 on cisplatin-induced cardiotoxicity by alleviating oxidative stress and mitochondrial dysfunction

“…Evidence has shown that cisplatin chemotherapy can lead to cardiotoxicity (8,26). This is in agreement with the present study where cisplatin significantly inhibited cell viability and induced apoptosis of rat cardiomyocytes.…”

“…Cardiomyocytes are mitochondria-rich cells. Cardiac mitochondrial dysfunction often occurs upon ROS accumulation and overproduction caused by cisplatin, which results in disruption of mitochondrial membrane potential and release of pro-apoptotic factor (8). In the present study, loss of ΔΨm and release of cyto-c into cytosol were observed in rat cardiomyocytes treated with cisplatin.…”

“…In the present study, loss of ΔΨm and release of cyto-c into cytosol were observed in rat cardiomyocytes treated with cisplatin. Cyto-c translocation into the cytosol often precedes ΔΨm loss and is regarded as a sign of severe mitochondrial damage (34), which can subsequently induce caspase-dependent apoptosis of cardiomyocytes (8,26). However, these disruptions caused by cisplatin can be improved by TMZ and CoQ10, suggesting that TMZ and CoQ10 may inhibit cell apoptosis partially through suppressing cisplatin-induced mitochondrial dysfunction.…”

“…Oxidative stress is considered to be one of the major mechanisms involved in cisplatin-induced cardiotoxicity, as characterized by reactive oxidative species (ROS) production, lipid peroxidation, and inhibition of antioxidant enzymes such as glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) (5-7). On the other hand, excessive ROS can target mitochondria, result-ing in mitochondrial dysfunction and release of cytochrome c (cyto-c) into the cytosol, which can subsequently induce caspase-dependent apoptosis (1,8,9). Hence, we hypothesize that timely intervention on oxidative stress may be an effective measure to prevent against cisplatin-induced cardiotoxicity.…”

Platycodin D protects acetaminophen-induced hepatotoxicity by inhibiting hepatocyte MAPK pathway and apoptosis in C57BL/6J mice

“…Excessive ROS accumulation would damage cellular macromolecules such as proteins through activation of a series of signaling cascades, including mitochondrial, apoptotic and PI3K/Akt pathways [27]. When cisplatin accumulates in the mitochondrial matrix, it causes a large amount of ROS production and mitochondrial dysfunction, leading to increased mitochondrial permeability, pro-apoptotic factor release and initiate apoptosis [29]. The Bcl-2 family of proteins has a crucial role in the apoptotic mechanism of mitochondrial pathway [30], which includes pro-apoptotic protein Bax and antiapoptotic protein Bcl-2 [31].…”